Collagen, the major structural protein of the periodontium, is disorganized and lost during periodontal disease. We have found that diabetes affects the collagen metabolism and collagenase activity of rat gingiva explaining, in part, the accelerated periodontal breakdown and delayed wound healing associated with this systemic factor. Objectives of the proposed project are: (1) to expand our studies elucidating the effects of diabetes on collagen metabolism of uninflamed and inflamed gingiva of rats, and (11) to determine whether changes in the rat model hold true for gingival tissues of human diabetics. The animal studies will examine diabetic alterations in (a) gingival collagen biosynthesis, including prolyl and lysyl hydroxylase activity and the formation of H3-hydroxyproline in vivo; (b) the relative amounts of type I and type III collagens in gingiva; (c) gingival collagen maturation, including lysyl oxidase activity and the solubility of H3-hydroxyproline labeled collagen formed in vivo. In addition, germ-free rats will be made diabetic to determine whether the diabetes-induced changes in gingival collagen metabolism are a direct effect, mediated by alterations in tissue metabolism, or in indirect effect, resulting from an altered oral microflora. Gingival tissue from systemically-normal and diabetic human subjects (removed during periodontal surgery for therapeutic reasons) will be analyzed for soluble and insoluble collagen content; other samples will be cultured to examine collagen turnover and collagenase activity in vitro. Gingival fluid collagenase activity will be monitored in these subjects before, and at various times after surgery and will be correlated to collagen changes in the adjacent gingival tissue.